Regulation of cardiac glycogen synthase

In perfused rat hearts insulin can activate, and catecholamines can inactivate, glycogen synthase (EC 2.4.1.11); the magnitude of each hormonal response is magnified if tissue glycogen levels are depleted. Both beta-adrenergic and alpha-adrenergic agonists inactivate insulin-stimulated and basal glycogen synthase, with each promoting the same extent of inactivation in both circumstances. In this system beta-adrenergic agonists act via cyclic AMP (cAMP), and alpha-adrenergic agonists via Ca2+, whereas insulin action appears to be independent of either cAMP or Ca2+. The action on cardiac glycogen synthase by the physiological catecholamine epinephrine is apparently mediated by the concomitant interaction with both alpha and beta receptors; interaction with each is mediated by their separate second messenger systems, which combine to produce the end physiological response.